title: The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment.
abstract: OBJECTIVE
  Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo.
  
  
  METHODS
  Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo.
  
  
  RESULTS
  When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased.
  
  
  CONCLUSIONS
  Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. t.n.deboer-4@umcutrecht.nl
authors.forename: T N
authors.initials: TN
authors.lastname: de Boer
authors.forename: A M
authors.initials: AM
authors.lastname: Huisman
authors.forename: A A
authors.initials: AA
authors.lastname: Polak
authors.forename: A G
authors.initials: AG
authors.lastname: Niehoff
authors.forename: A C
authors.initials: AC
authors.lastname: van Rinsum
authors.forename: D
authors.initials: D
authors.lastname: Saris
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: F J P G
authors.initials: FJ
authors.lastname: Lafeber
authors.forename: S C
authors.initials: SC
authors.lastname: Mastbergen
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011509:Proteoglycans / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D011509:Proteoglycans; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin